A Prospective Phase III Trial to Compare Stereotactic Radiosurgery Versus Whole Brain Radiation Therapy

Inclusion Criteria:

1. All patients must have histological proof of malignant cancer, which is metastatic. Histological proof may be obtained from the primary tumor or another metastatic site. However, cytology alone is not an acceptable method of diagnosis.
2. All patients must have greater than 3 but less than or equal to 10 metastatic lesions seen on a contrast enhancing MRI scan obtained not less than one month prior to study enrollment. Patients who are found to have 11-15 metastatic lesions at the time of treatment planning (on volumetric MRI once the head frame is in place) may still participate in the trial.
3. All patients must be >/= 18 years of age.
4. All patients must sign informed consent verifying that they are aware of the investigational nature of this study in keeping with the rules and policies of M.D. Anderson Cancer Center. The only acceptable consent form is the one attached at the end of this protocol, and it must have been approved and amended by the M.D. Anderson IRB.
5. All patients must be eligible to have all lesions treated with SRS (i.e. maximum diameter of largest lesion < 3.5cm) as determined by the study radiation oncologist .
6. All patients must have adequate liver, renal, and hematologic function as defined by Aspartate Amino Transferase (AST)/Alanine Amino Transferase (ALT)/Alkaline Phosphatase < 2.5 times normal, calculated creatinine clearance > 30ml/min, and platelet count > 50,000.
7. All patients should have normal coagulation, with international normalized ratio (INR) < 1.3 and able to withhold anti-coagulation medications a minimum of 24 hours prior to radiosurgery (or until INR normalizes), on the day of treatment and 24 hours after radiosurgery has concluded. Those patients getting WBRT may continue these medications.
8. Patients can be undergoing concurrent systemic therapy, such as temozolomide, at the discretion of their treating oncologist.

Exclusion Criteria:

1. Patients are excluded from this trial if they have melanoma, small cell carcinoma, lymphoma/leukemia, or germ cell histology (note, melanoma patients will be eligible for the sister trial to this trial which will be open simultaneously).
2. Patients will be excluded if they have had prior surgical resection of metastatic cancer from the brain.
3. Patients will be excluded if there are one or more lesions in the brainstem.
4. Patients will be excluded if there is radiographic or CSF cytological evidence of leptomeningeal disease.
5. Patients will be excluded if they have had prior radiation to the brain (either WBRT, prophylactic cranial irradiation (PCI), or SRS).
6. Female patients of childbearing age will be excluded if they are pregnant as assessed by serum b-HCG or urine pregnancy test. A serum b-HCG test or urine pregnancy test will be performed no greater than 14 days prior to study registration.
7. Patients will be excluded if they are unable to obtain an MRI scan.
8. Patients will be excluded if they have < 4 lesions, or > 10 lesions at enrollment or > 15 lesions at the time of treatment (note: patients who qualify for enrollment based on having 4-10 lesions, but who are discovered to have 11-15 lesions on the volumetric MRI used for treatment planning will be allowed to continue on study).