Inclusion Criteria:

1. Patients requiring a 3 week course of fractionated whole brain radiation therapy for brain metastases.
2. Age > or = 18
3. Histological or cytological diagnosis of a malignancy.
4. Patients who have only 1-3 metastases are frequently treated with stereotactic radiation. Nonetheless, if the treating physician decides that whole brain radiotherapy is the appropriate treatment such patients would be eligible to enroll upon in the study.
5. Radiographic evidence of brain metastasis.
6. Measurable disease preferred but not required for eligibility
7. Patient must have performance status of < or = 2 on the ECOG Performance Scale.
8. Life expectancy of > or = 3 months
9. Resolution of all acute toxic effects of prior chemotherapy or radiotherapy or surgical procedures to NCI CTCAE Version 3.0 grade < or = 1.

10. Adequate organ function as defined by the following criteria:

    • Serum aspartate transaminase (AST; serum glutamic oxaloacetic transaminase [SGOT]) and serum alanine transaminase (ALT; serum glutamic pyruvic transaminase [SGPT]) < or = 2.5 x local laboratory upper limit of normal (ULN), or AST and ALT < or = 5 x ULN if liver function abnormalities are due to underlying malignancy
    • Total serum bilirubin < or = 1.5 x ULN
    • Absolute neutrophil count (ANC) > or = 1500/µL
    • Platelets > or = 100,000/µL
    • Hemoglobin > or = 9.0 g/dL
    • Serum calcium < or = 12.0 mg/dL
    • Serum creatinine < or = 1.5 x ULN
    • Potassium level within normal limits.
    • Magnesium level within normal limits.
11. Female patient of childbearing potential has a negative serum pregnancy test β-hCG within 72 hours prior to receiving the first dose of Vorinostat .
12. Female patient is either post menopausal, free from menses for > or = 2 years, surgically sterilized, or willing to use 2 adequate barrier methods of contraception to prevent pregnancy, starting with Visit 1.
13. Male patient agrees to use an adequate method of contraception for the duration of the study.
14. Ability to understand and the willingness to sign a written informed consent. A signed informed consent must be obtained prior to any study specific procedures.
15. INR < 1.5 or a PT/PTT within normal limits. Patients receiving anti-coagulation treatment with an agent such as warfarin or heparin may be allowed to participate. For patients on warfarin, the INR should be measured prior to initiation of Vorinostat and monitored at least weekly, or as defined by the local standard of care, until INR is stable.
16. Patient is available for study related assessments, and management at the treating institution, for the duration of the study.

Exclusion Criteria:

1. Previous cranial irradiation (whether whole or partial brain, single fraction or multiple fractions) within the previous six months.
2. Patient who has had chemotherapy within 21 days, non-cranial radiotherapy within 10 days, or who has not recovered from adverse events due to agents administered more than 30 days earlier.
3. Patient is currently participating or has participated in a study with an investigational compound or device within 14 days of initial dosing with study drug(s).
4. Patient has had prior treatment with an HDAC inhibitor (e.g., romidespin (Depsipeptide), NSC-630176, MS 275, LAQ-824, belinostat (PXD-101), LBH589, MGCD0103, CRA024781, etc). Patients who have received compounds with HDAC inhibitor-like activity, such as valproic acid, as anti-tumor therapy should not enroll in this study. Patients who have received such compounds for other indications, e.g. valproic acid for epilepsy, may enroll after a 30-day washout period under neurological supervision.
5. Patients with markedly elevated intracranial pressure.
6. Cardiac disease: Congestive heart failure > class II NYHA. Patients must not have unstable angina (anginal symptoms at rest) or new onset angina (began within the last 3 months) or myocardial infarction within the past 6 months.
7. Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy.
8. An extended QTc interval on baseline EKG examination. Normal values: male < 430ms, female <450 ms.
9. Concomitant use of medications known to extend the QTc interval: Quinidine, Procainamide, Disopyramide, Dofetilide, Ibutilide, Sotalol, Amiodarone, Bepridil, Cisapride, Macrolides, Erythromycin, Clarithromycin, Fluoroquinolones, Sparfloxacin, Antiprotozoals, Pentamidine, Antimalarials, Halofantrine, Chloroquine, Phenothiazine neuroleptics, Thioridazine, Chlorpromazine, Mesoridazine, Butyrophenone neuroleptics, Droperidol, Haloperidol, Diphenylpiperidine neuroleptics, Pimozide, Arsenic trioxide, Methadone, Cesium, Licorice, Zhigancao
10. Uncontrolled hypertension defined as systolic blood pressure > 150 mmHg or diastolic pressure > 90 mmHg, despite optimal medical management.
11. Known human immunodeficiency virus (HIV) infection or chronic Hepatitis B or C.
12. Active clinically serious infection > CTCAE Grade 2
13. NCI CTCAE grade 3 hemorrhage within 4 weeks of starting the study treatment.
14. Thrombolic or embolic events such as a cerebrovascular accident including transient ischemic attacks within the past 6 months.
15. Pulmonary hemorrhage/bleeding event > or = CTCAE Grade 2 within 4 weeks of first dose of study drug.
16. Serious non-healing wound, ulcer, or bone fracture.
17. Evidence or history of bleeding diathesis or coagulopathy
18. Major surgery, open biopsy or significant traumatic injury within 4 weeks of first study drug.
19. Use of St. John's Wort or rifampin (rifampicin).
20. Any condition that impairs patient's ability to swallow whole pills.
21. Any malabsorption problem.
22. Pregnancy or breastfeeding. Female subjects must be surgically sterile or be postmenopausal, or must agree to use effective contraception during the period of therapy. All female subjects with reproductive potential must have a negative pregnancy test (serum or urine) prior to enrollment. Male subjects must be surgically sterile or must agree to use effective contraception during the period of therapy. The definition of effective contraception will be based on the judgment of the principal investigator or a designated associate.
23. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment of the investigator would make the subject inappropriate for entry into this study.
24. Documented history of cranial hemorrhage
25. Patient has an active infection or has received intravenous antibiotics, antiviral, or antifungal agents within 2 weeks prior to the start of the study drug.
26. Patient has uncontrolled inter-current illness or circumstances that could limit compliance with the study, including, but not limited to the following: active infection, acute or chronic graft versus host disease, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric conditions.
27. Patient has a history or current evidence of any condition, therapy, or lab abnormality that might confound the results of the study, interfere with the patient's participation for the full duration of the study or is not in the best interest of the patient to participate.
28. Patient has a history of a gastrointestinal surgery or other procedures that might, in the opinion of the investigator, interfere with the absorption or swallowing of the study drugs.
29. Patient has known hypersensitivity to the components of study drug or its analogs.
30. Patient has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
31. Patient is, at the time of signing informed consent, a regular user (including "recreational use") of any illicit drugs, substance abuse or had a recent history (within the last year) of drug or alcohol abuse.
32. Patient is pregnant or breast feeding, or expecting to conceive or father children within the projected duration of the study.