Inclusion Criteria:

1. Histologic Documentation: Histologic or cytologic diagnosis of distant metastatic melanoma and clinical evidence of brain metastasis.
2. Pts must have brain lesions of =/> 1.0cm longest dimension by MRI or spiral CT, if MRI not feasible or > 0.5cm by MRI with 3D images. Pts with/without extracranial disease are eligible. Measurable extracranial disease is not required. Lesions that are considered non-measurable include: <1.0 cm by MRI or Spiral CT, Bone lesions, Leptomeningeal disease, Ascites, Pleural/pericardial effusion, Lymphangitis cutis/pulmonis, Abdominal masses that are not confirmed and followed by imaging techniques, Cystic lesions, lesions that are in a previously irradiated area, unless new growth can be documented.
3. Age >/= 18 years of age.
4. ECOG Performance Status: 0 or 1
5. No more than 1 prior chemotherapy regimen and no prior chemotherapy for brain metastases. No prior treatment with continuous daily dose of temozolomide; prior immunotherapy and surgical resection are permitted. Patients with prior history of whole brain radiotherapy (WBRT) and stereotactic radiosurgery (SRS) are permitted providing that there is measurable lesion with documented growth post radiation or new disease.
6. (#5 contd) Progression of lesions treated with WBRT must be shown by 2 post treatment brain imaging at least 3 weeks apart. Progression of disease is also considered when the patient had increase of lesions as per MRI of brain obtained 4 weeks or more after WBRT completed when compared to baseline MRI obtained less than 1 week prior to start of radiation. Lesions treated with SRS must have responded and then progressed.
7. The following time periods must have elapsed since prior therapy: 3 weeks since surgical resection or stereotactic radiosurgery; 4weeks since prior whole brain radiation therapy; 6 weeks since prior nitrosureas or mitomycin C. Biologic agents used as adjuvants and vaccines or cellular therapies will not require 4-week wash out period if the patient meets all eligibility criteria.
8. No frequent vomiting and/or medical condition that could interfere with oral medication intake (e.g., partial bowel obstruction).
9. No other concurrent chemotherapy/immunotherapy/radiotherapy.
10. No history of active angina or myocardial infarction within 6 months. No history of significant ventricular arrythmia or uncontrolled arrythmia or bradycardia. The study participants must have resting heart rate of 48 or greater (.e.i - to receive Thalidomide).
11. No prior history of deep vein thrombosis (DVT) or pulmonary embolism (PE).
12. No known HIV disease. Patients with a history of intravenous drug abuse or any other behavior associated with an increased risk of HIV infection should be tested for exposure to the HIV virus. Because peripheral neuropathies are a common toxicity of antiviral therapy and of viral infection in HIV patients, as well as a common significant toxicity with thalidomide, patients who test positive or who are known to be infected are not eligible. An HIV test is not required for entry on this protocol, but is required if the patient is perceived to be at risk.
13. No pre-existing neuropathy that is >/= grade 2, including uncontrolled seizures.
14. No expected need for radiotherapy to brain or any extracranial metastatic site during the period of participation in the study.
15. Patients may not be taking Coumadin, warfarin or heparin products or their derivatives.
16. Patients who require anti-platelet therapy such as daily aspirin, Plavix or ibuprofen are not eligible to participate.
17. Patients requiring the use of bisphosphonates (e.g., zolendronic acid) are not eligible to participate. Patients who receive thalidomide in combination with zolendronic acid are potentially at increased risk of renal dysfunction.
18. Required Initial Laboratory Data: Granulocytes >/= 1,500/ml; Platelet count >/= 100,000/ul; Creatinine </=2 mg/dl; Transaminases (ALT,AST) </= 3 x upper limits of normal; Alkaline phosphatase </= 3 x upper limits of normal; TSH Within normal limits Serum beta-HCG Negative (in female patients unless S/P hysterectomy or menopausal or no menses for 24 months). Assay must have a sensitivity of at least 50 mIU/ml. Serum anticonvulsant levels (for patients on a measurable anticonvulsant) must be within therapeutic range. EKG must be without acute abnormalities or uncontrolled arrhythmia.
19. Pregnant and nursing women are not eligible for treatment on this protocol. Women of childbearing potential must agree to abstain from all intercourse or use two methods of birth control for 28 days prior to treatment and while under treatment with thalidomide and for 4 weeks after completing therapy. One of the methods of birth control must be highly active (IUD, hormonal, tubal ligation or partner's vasectomy) and used concomitantly with one additional method(e.g., latex condom, diaphragm or cervical cap. Please see also eligibility criteria 19 and 20.
20. In addition, women of childbearing potential must have morning urine b-HCG performed within 1 week prior to registration and within 24 hours before beginning study treatment. All the precautions for childbearing potential women are required even in patients with infertility unless due to hysterectomy or the patient has been post menopausal (has had no menses for at least 24 consecutive months). Men must agree to abstain from unprotected sexual intercourse. Male patients should request that female partners use a second method of birth control in addition to the male barrier method (condoms).
21. All patients (men and women) must agree to use medically approved contraceptive measures simultaneously prior to starting thalidomide therapy, all during drug therapy, and for at least 1 month after therapy has stopped. Women of childbearing potential should start using medically approved contraceptive measures 4 weeks prior to starting thalidomide therapy.
22. Patients must give written consent.
23. Patients must be willing and able to comply with the FDA-mandated S.T.E.P.S version 3 program.

Exclusion Criteria:

1. Presence of any ongoing toxic effect from prior treatment.
2. Serious infection requiring intravenous antibiotics, or nonmalignant medical illnesses that are uncontrolled or whose control may be jeopardized by the complications of this therapy.
3. Concurrent active malignancy other than non-melanoma skin cancers or carcinoma-in-situ of the cervix. Patients with previous malignancies, but which have not required anti-tumor treatment within the preceding 24 months will be allowed to enter the trial. Patients with a history of a T1a or b prostate cancer (detected incidentally at TURP and comprising less than 5% of resected tissue) may participate if the PSA remained within normal limits since TURP.
4. Any other medical condition or reason that, in the principal investigator's opinion, makes the patient unsuitable to participate in a clinical trial including but not limited to active bleeding, prior surgical procedures affecting absorption or gastrointestinal tract disease resulting in inability to take oral medication.
5. Pregnant and lactating women.