Have evidence of any other significant clinical disorder or laboratory finding that, as judged by the investigator, makes it undesirable for the patient to participate in the study Uncontrolled or progressive systemic disease or other concurrent condition which in the Investigators opinion makes HD-MTX an undesirable treatment option for the patient or would jeopardize compliance Active bleeding diatheses, which in the investigators opinion makes it undesirable for the patient to participate in the trial or which would jeopardize compliance with the protocol Any evidence of severe or uncontrolled systemic diseases, including active bleeding diatheses, which in the investigators opinion makes it undesirable for the patient to participate in the trial or which would jeopardize compliance with the protocol Any serious and/or unstable pre-existing medical, psychiatric, or other condition (e.g., severe hepatic impairment) or current unstable or uncompensated respiratory or cardiac conditions which makes it undesirable for the patient to participate in the study or which could jeopardize compliance with the protocol. No evidence of severe or uncontrolled other systemic disease or any concurrent condition which in the investigators opinion makes it undesirable for the subject to participate in the trial or which would jeopardize compliance with the protocol Any concurrent condition which in the investigators opinion makes it undesirable for the subject to participate in this trial or which would jeopardize compliance with the protocol Any evidence of severe or uncontrolled systemic conditions (e.g., severe hepatic impairment) or current unstable or uncompensated respiratory or cardiac conditions which makes it undesirable for the patient to participate in the study or which could jeopardize compliance with the protocol Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension and active bleeding diatheses, which in the investigators opinion makes it undesirable for the patient to participate in the trial or which would jeopardize compliance with the protocol; screening for chronic conditions is not required Evidence of severe or uncontrolled systemic disease or any concurrent condition which in the Investigators opinion makes it undesirable for the patient to participate in the trial or which would jeopardize compliance with the protocol Evidence of any significant clinical disorder or laboratory finding that makes it undesirable for the subject to participate in the clinical trial Serious uncontrolled medical disorder or uncontrolled active systemic infection or current unstable or decompensated respiratory or cardiac conditions which makes it undesirable or unsafe for the patient to participate in the study Any evidence of severe or uncontrolled systemic diseases, including, but not limited to, uncontrolled hypertension, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations which in the investigators opinion makes it undesirable for the patient to participate in the trial or which would jeopardize compliance with the protocol, or active infection including hepatitis B, hepatitis C and human immunodeficiency virus (HIV); screening for chronic conditions is not required Any evidence of severe or uncontrolled systemic or psychiatric diseases, including uncontrolled hypertension and active bleeding diatheses, which in the Investigator's opinion makes it undesirable for the patient to participate in the trial or which would jeopardize compliance with the protocol Evidence of severe or uncontrolled systemic disease or any concurrent condition which in the investigators opinion makes it undesirable for the patient to participate in the trial or which could jeopardize compliance with the protocol Evidence of any other significant clinical disorder or laboratory finding that makes it undesirable for the subject to participate in the clinical trial Evidence of severe or uncontrolled systemic disease or any concurrent condition that, in the opinion of the Investigator or Medical Monitor, makes it undesirable for the subject to participate in the study or that would jeopardize compliance with the protocol. Subjects with pre-existing well-controlled diabetes are not excluded. Evidence of any other significant clinical disorder or laboratory finding that makes it undesirable for the subject to participate in the trial Patients with any other medical condition or reason, in that investigators opinion, makes the patient unstable to participate in a clinical trial Evidence of any other significant clinical disorder or laboratory finding that makes it undesirable for the patient to participate in the trial Any concurrent condition which in the investigators opinion makes it undesirable for the subject to participate in this trial or which would jeopardize compliance with the protocol Patients with any clinically significant medical condition which, in the opinion of the investigator, makes it undesirable for the patient to participate in the study or which could jeopardize compliance with protocol requirements including, but not limited to: ongoing or active infection, significant uncontrolled hypertension, or severe psychiatric illness/social situations Evidence of severe or uncontrolled systemic disease or any concurrent condition including, but not limited to symptomatic congestive heart failure, unstable angina pectoris, unstable hypertension, seizure disorder, or psychiatric illness which in the Investigators opinion makes it undesirable for the patient to participate in the trial or which would jeopardize compliance with the protocol Any concurrent condition which in the investigator's opinion makes it undesirable for the patient to participate in the trial or which would jeopardize compliance with the protocol. Evidence of any other significant clinical disorder or laboratory finding that makes it undesirable for the patient to participate in the trial. Evidence of any significant clinical disorder or laboratory finding that makes it undesirable for the subject to participate in the clinical trial Evidence of severe or uncontrolled systemic disease or any concurrent condition which in the investigators opinion makes it undesirable for the patient to participate in the trial or which would jeopardize compliance with the protocol