Phase II Study of Gamma Knife Radiosurgery and Temozolomide for Brain Metastases

Inclusion Criteria:

* All subjects must have history of histologically confirmed malignancy. Brain biopsy is not required unless diagnosis is judged to be in doubt by the treating physician.
* Newly diagnosed brain metastases (four or fewer by thin slice post-contrast MRI).
* ECOG performance status of less than or equal to 2 for patients with no prior chemotherapy, and less than or equal to 1 for patients with prior chemotherapy.
* Age greater than 18
* Life expectancy greater than 12 weeks
* Subjects given written informed consent
* Adequate hematologic, renal and liver function as demonstrated by laboratory values performed within 14 days, inclusive, prior to administration of study drug:

  * Absolute neutrophil count (ANC) \>= 1500/mm3
  * Platelet count \>= 100,000/mm3
  * Hemoglobin \>= 9 g/dL
  * BUN and serum creatinine \<= 1.5 times upper limit of laboratory normal
  * Total and direct bilirubin \<= 2 times upper limit of laboratory normal or in the presence of documented liver metastases, total and direct bilirubin \<=5 times upper limit of normal
  * SGOT and SGPT \<= 2 times upper limit of laboratory normal or in the presence of documented liver metastases, SGOT and SGPT \<=5 times upper limit of normal
  * Alkaline phosphatase \<= 2 times upper limit of laboratory normal or in the presence of documented liver metastases, alkaline phosphatase of \<= 5 times upper limit of normal

Exclusion Criteria:

* Patients with small cell lung cancer and lymphoma are ineligible.
* More than four metastases by thin slice MRI. Note that if a diagnostic study prior to radiosurgery demonstrates only four tumors but the gamma knife treatment-planning scan reveals greater than four tumors, the patients will still be eligible for the protocol if all tumors can be treated with radiosurgery.
* Chemotherapy within four weeks prior to study drug administration
* Patients, who in the opinion of the treating medical oncologist, require immediate cytotoxic chemotherapy other than the study drug. Allowed medications include antihormonal agents (i.e., Tamoxifen), herceptin and bisphosphonates.
* Radiation therapy to greater than or equal to 50% of the bone marrow. Completion of radiation therapy less than 4 weeks prior to study drug administration for radiotherapy to \>= 15% of bone marrow and less than 2 weeks prior for radiotherapy to \< 15% of bone marrow.
* Insufficient recovery from all active toxicities of prior therapies
* Subjects who are poor medical risks because of non-malignant systemic disease
* Frequent vomiting or medical condition that could interfere with oral medication intake (e.g., partial bowel obstruction).
* Previous or concurrent malignancies at other sites, or treatment for malignancy at the site within 5 years of study start with the exception of surgically cured carcinoma in-situ of the cervix and basal or squamous cell carcinoma of the skin.
* Known HIV positively or AIDS-related illness.
* Pregnant or nursing women.
* Women of childbearing potential who are not using an effective method of contraception. Women of childbearing potential must have a negative serum pregnancy test 24 hours prior to administration of study drug and be practicing medically approved contraceptive precautions.
* Men who are not advised to use an effective method of contraception.