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The presenting clinical manifestations of a newly detected brain mass can assist the admitting physician in differentiating between tumor and other etiologies. In a patient with imaging features that are highly suggestive of a malignant primary brain tumor, it is reasonable to proceed directly to brain biopsy or craniotomy after a very limited systemic workup. Glioblastomas (GBM) is the most common primary brain tumor with which hospitalists will be involved. The three components of initial, or upfront, treatment for the patient with GBM are maximal safe debulking surgery, involved field irradiation (RT), and chemotherapy. Systemic cancers usually involve the central and peripheral nervous system through direct metastasis or by compression of neural tissue by metastatic disease in adjacent structures. The abundant vasogenic edema that surrounds many brain tumors may be a significant cause of the symptoms such as headache and focal neurological deficits.