Assume you have a PDF document open in another program (like Adobe Acrobat or Microsoft Word). If you try rename that same file in the Open dialogue box just before uploading the file to the site while you still have it open, you will likely get a "File in Use" notice from their operating system (as shown below).
A person's first instinct would be to close the PDF document and click "Try Again", but this will produce another error. The filename will change on your computer, but the efile system will still try to upload the document with the original filename, prompting the following error message: "File Must Not Be Empty."
To resolve the error, simply upload the newly-renamed file to your filing envelope.